Immunologic factors influence the clinical course of cancer. We propose to study the effect of some of these factors on an early stage of metastasis, namely their influence on the pattern of circulating tumor cell arrest and attachment to vascular endothelium. These studies will focus on two main topics, firstly, the distribution of isotopically-labelled tumor cells injected into mice with clearly defined immunologic status with respect to their tumor. The tumor-immune status of mice will be analyzed by in vitro cytotoxicity tests designed to assess the cytotoxic activity of lymphocytes and serum against tumor cells, and also the abrogation of cell-mediated immune reactions of serum "blocking factors". Sites of initial tumor cell arrest will be compared with the quantity and pattern of metastases arising after injection of unlabelled cells. Secondly, we propose to examine the possible interactions between platelets, tumor cells and immunologic factors, in an attempt to determine the role immunologic factors may play in the mechanisms of platelet-mediated tumor cell arrest. These interactions will be measured by assaying the ability of tumor cell/immunologic factors to elicit platelet activation reactions characteristic of thrombus formation, such as platelet aggregation, adhesiveness to inert surfaces and release of isotopically-labelled intracellular constituents. We also propose to correlate these findings with ultrastructural aspects of platelet-tumor cell and vascular endothelium interactions.